DNA methylation is an important epigenetic modification in mammals, playing a crucial role in various physiological processes, including cell differentiation and the gene expression regulation. The ten-eleven translocation (TET) protein family of DNA demethylases is integral to the regulation of DNA methylation, as it catalyzes the oxidation of 5-methylcytosine to form 5-hydroxymethylcytosine. During early embryonic development, the genome undergoes extensive DNA demethylation, and any aberration in this reprogramming process can result in abnormal embryonic development and physiological defects in offspring. The TET proteins, due to their unique dynamics and multifaceted roles, facilitate DNA demethylation and are involved in development and maturation of germ cells, the establishment of pluripotency, cell lineage differentiation, and transcriptional processes throughout mammalian embryogenesis. Furthermore, these proteins are closely associated with the maintenance of pregnancy and susceptibility of progeny to disease. Factors such as genetic mutations, maternal health conditions, and exposure to adverse environmental influences can impact TET protein activity, resulting in abnormal patterns of DNA demethylation. A comprehensive investigation of the related mechanisms of TET proteins is essential for enhancing our understanding of epigenetic regulation during early life, diagnosing and treating related diseases such as early fetal development retardation, and informing strategies for the prevention and management of pregnancy.This article reviews the regulatory role of DNA demethylation mediated by TET protein in mammalian embryonic development and pregnancy outcomes.

DNA methylation is an important epigenetic modification in mammals, playing a crucial role in various physiological processes, including cell differentiation and the gene expression regulation. The ten-eleven translocation (TET) protein family of DNA demethylases is integral to the regulation of DNA methylation, as it catalyzes the oxidation of 5-methylcytosine to form 5-hydroxymethylcytosine. During early embryonic development, the genome undergoes extensive DNA demethylation, and any aberration in this reprogramming process can result in abnormal embryonic development and physiological defects in offspring. The TET proteins, due to their unique dynamics and multifaceted roles, facilitate DNA demethylation and are involved in development and maturation of germ cells, the establishment of pluripotency, cell lineage differentiation, and transcriptional processes throughout mammalian embryogenesis. Furthermore, these proteins are closely associated with the maintenance of pregnancy and susceptibility of progeny to disease. Factors such as genetic mutations, maternal health conditions, and exposure to adverse environmental influences can impact TET protein activity, resulting in abnormal patterns of DNA demethylation. A comprehensive investigation of the related mechanisms of TET proteins is essential for enhancing our understanding of epigenetic regulation during early life, diagnosing and treating related diseases such as early fetal development retardation, and informing strategies for the prevention and management of pregnancy.This article reviews the regulatory role of DNA demethylation mediated by TET protein in mammalian embryonic development and pregnancy outcomes.

Objective To evaluate the bioequivalence of two formulations of minocycline hydrochloride capsules administered orally after fasting administration and fed administration.Methods An open-label,randomized,two-period,self-crossover design was employed to assess the bioequivalence study.Twenty-eight healthy subjects were enrolled in both fasting and fed groups,with each period involving a single administration of either the reference formulation or the test formulation of 50 mg,separated by a washout period of 7 days.The concentration of minocycline in human plasma was determined by HPLC-MS/MS and was used for calculating pharmacokinetic parameters and evaluating the bioequivalence of the test formulation and reference formulation.Results After oral administration of test and reference formulations of minocycline under fasting condition,the Cmax Values of minocycline were(541±137)ng·mL-1 for the test formulation and(558±140)ng·mL-1for the reference formulation.The AUC0-t values were(8 347±1 986)h·ng·mL-1 for the test and(8 205±1 790)h·ng·mL-1 for the reference.The t1/2 values were(18.2±2.84)h for the test and(18.0±3.05)h for the reference.After oral administration of the test and reference formulations of minocycline under fed condition,the Cmax values of minocycline were(349±72.1)ng·mL-1 for the test and(352±73.2)ng·mL-1for the reference.The AUC0-twere(6 428±1 077)h·ng·mL-1 for the test and(6 588±1 118)h·ng·mL-1 for the reference.The t1/2values were(18.5±3.10)h for the test and(18.4±3.21)h for the reference.Under fasting condition,the 90% confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ between the test and reference formulations were(90.84%,101.46% ),(95.2%,102.8% ),and(95.31%,102.71% ),respectively.Under fed conditions,the 90% confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ between the test formulation and the reference formulation were(94.71%,103.42% ),(95.40%,99.83% ),and(95.79%,100.02% ),respectively.Conclusions Bioequivalence of the two minocycline formulations was demonstrated after fasting administration and fed administration in a healthy Chinese population.

Objective:To investigate the risk factors of bone cement leakage after percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fracture (OVCF).Methods:A multi-center, large-sample, case-control study was carried out to analyze the clinical data of 2 273 OVCF patients (2 689 vertebrae) undergone PVP at four hospitals between May 2018 and October 2021, including 994 males and 1 279 females, with the age of 52-91 years [(69.1±3.1)years]. Of all, 581 patients (604 vertebrae) were allocated to leakage group and 1 692 patients (2 085 vertebrae) to no leakage group according to the occurrence of bone cement leakage. The gender, age, fracture sites, vertebral compression degree, endplate integrity of fractured vertebrae, surgical segments, surgical approaches and bone cement injection volume were recorded. Univariate analysis was used to investigate the correlation between those indicators with bone cement leakage. Multivariate Logistic regression analysis was used to identify the independent risk factors for bone cement leakage.Results:Univariate analysis showed that gender, age, fracture sites, vertebral compression degree, bone cement injection volume were related to bone cement leakage after PVP ( P<0.05 or 0.01), but no correlation was found in the endplate integrity of fractured vertebrae, surgical segments and surgical approaches (all P>0.05). Multivariate Logistic regression analysis showed that fracture sites ( OR=1.68, 95% CI 1.11-2.55, P<0.05), vertebral compression degree more than 40% ( OR=1.98, 95% CI 1.29-3.02, P<0.01), bone cement injection volume greater than or equal to 5.5 ml ( OR=1.55, 95% CI 1.07-2.26, P<0.05) were significantly associated with bone cement leakage after PVP. Conclusion:Thoracic vertebral fracture, vertebral compression degree more than 40% and bone cement injection volume greater than or equal to 5.5 ml are independent risk factors for bone cement leakage after PVP in OVCF.

Objectives:To investigate the value of histopathological growth patterns (HGP) in predicting the 3-year progression free survival (PFS) after resection the liver metastasis from patients with colorectal cancer.Methods:The clinicopathological data of the 111 patients with liver metastasis of colorectal cancer diagnosed at Peking University People′s Hospital, Beijing, China from January 2007 to January 2017 were analyzed. After excluding the patients who did not meet the inclusion criteria, a total of 80 patients were analyzed. According to the international expert consensus on HGP, the HGP types of liver metastasis were evaluated. The correlation between HGP and other clinicopathological factors was analyzed using χ 2 or Fisher test. Kaplan-Meier survival curve was used to examine 3-year PFS in the patients with liver metastasis of colorectal cancer by HGP. The independent risk factors of 3-year post-resection PFS were determined using univariable and multivariable analyses. Results:A total of 80 cases were analyzed, including 43 cases of desmoplastic type (54%), 32 cases of replacement type (40%), 3 cases of pushing type (4%), and 2 cases of mixed type (2%). There was no correlation of HGP with age, gender, time of metastasis, tumor burden, histological grade, mucous differentiation or microsatellite instability. The 3-year post-resection PFS of the patients with desmoplastic type was significantly longer than that of patients with replacement type. The univariable and multivariable analyses showed that HGP was an independent prognostic factor.Conclusions:The HGP of colorectal cancer metastases to the liver mainly present as desmoplastic and replacement types. HGP is an independent prognostic factor for the patients with liver metastasis of colorectal cancer after resection of the metastasis. Therefore, HGP should be clearly indicated in the pathological report to help guide clinical treatments.

Objective To compare the effectiveness of 3D cervical spine versus titanium mesh cage in the treatment of fractures of lower cervical vertebrae.Methods From May 2016 to March 2017,a total of 31 patients with cervical spine fracture were enrolled in this prospective randomized controlled trial at Department of Orthopaedics,Luohe Central Hospital.Of them,16 cases were randomized to receive anterior cervical sub-total resection and decompression followed by internal fixation with implant of 3D printed cervical spine (3D group) and 18 to receive anterior cervical sub-total resection and decompression followed by internal fixation with implant of titanium mesh cage (TM group).The 2 groups were compared in terms of operation time,intraoperative bleeding,score and improvement rate of Japanese Orthopaedic Association (JOA),vertebral height change,cobb angle change and bone graft fusion.Results Eventually,included for this study were 15 cases in the 3D group and 16 in the TM group who had been completely followed up.Operations were well done for all the patients.The operation time for the 3D group (83.9 ± 21.4 min) was significantly shorter than that for the TM group (116.2 ± 27.8 min) (t =5.039,P ＜ 0.001).There was no significant difference between the 2 groups in intraoperative bleeding (92.6 ± 25.4 mL versus 105.6 ± 21.7 mL) (t =0.950,P =0.350).Follow-ups for 6 to 15 months revealed no implants failure or displacement in either group.By the final follow-up,bony union was achieved in all.Their preoperative JOA scores were all improved at the final follow-ups.There was no significant difference in JOA scores between the 2 groups (P ＞0.05).The vertebral heights and cobb angles at postoperative 3 months and at the final follow-up in the 3D group were significantly larger than those in the TM group (P ＜ 0.05);the vertebral heights and cobb angles at postoperative 3 months and at the final follow-up were significantly improved than the preoperative values in all the patients (P ＜ 0.05);there was no significantly difference between the vertebral height and cobb angle at postoperative 3 months and those at the final follow-up in either group (P ＞ 0.05).The incidence of prosthesis settlement in the 3D group (6.7％) was significantly lower than that in the TM group (43.75％)(P ＜ 0.05).Conclusions Both surgical procedures can reconstruct cervical stability.Compared with titanium mesh cage,3D printed cervical spine may lead to shorter operation time,better bone-material bonding interface,less prosthesis sinking and superiority in maintaining the cervical height and curvature.

Objective Compare the clinical efficacy between anterior cervical decompressions, internal fixation with steel plate and zero profile interbody fusion system (Zero-P) in the treatment of cervical spondylotic myelopathy.Methods From October 2010 to May 2013, a total of 47 patients with cervical myelopathy were included in prospective randomized controlled study.All patients were randomly divided into two groups, respectively using plate fixation (screw plate system group, 26 cases)and Zero-P (Zero-P group, 21 cases).Compared operation time, intraoperative blood loss, postoperation flow and the incidence of postoperative discomfort swallowing.Evaluated the Japanese Orthopaedic Association (JOA) score of nerve function and calculated improvement rate;measured cervical Cobb Angle on X-ray film, observed abnormal activity of surgical clearance, evaluated degree of bone graft fusion and related internal fixation complications.Results The average operation time of screw plate system group was 71.2±26.8 min, which was 53.4±28.6 min in Zero-P group, significant difference was found in two groups.The average bleeding volume was 78.1 ±46.7 ml, and average volume of postoperation drainage was 63.3±37.7 ml in screw plate system group;the average bleeding volume was 77.5±50.4 ml, and the average volume of postoperation drainage was 60.7±28.6 ml in Zcro-P group, no significant difference was found.5 cases in screw plate system group remained swallowing discomfort 3 weeks after operation, but non in Zero-P group.Followed-up lasted for 24-42 months, an average of 23±2.16 months, nerve function were significantly improved at the end of the follow-up of both two groups, the JOA score of screw plate system group was 14.28±2.96, the improvement rate was 68.91％±7.9％, and Zero-P group was 14.32±2.87, the improvement rate was 69.79％±11.2％, there were no significant difference;curvature of cervical vertebrae of screw plate system group was 15.2°±5.7° at the end of follow-up;Zero-P group was 18.1°±7.9°, which with significant difference.Bone graft fusion were found in all patients at the end of follow-up, and no abnormal activities and fixation loosening was found during follow-up period.Conclusion Zero-P compared with traditional fracture-fixation techniques in treating single or double segments of cervical spondylotic myelopathy, can shorten operation time, reduce the incidence of postoperative chronic discomfort swallowing, and maintain in favour of cervical curvature.